title: Ancillary testing of liquid-based cytology specimens for identification of patients at high risk of cervical cancer.
abstract: Integration of human papillomavirus DNAs into the host genome is crucial to the development of cervical cancer. Overexpression of the P16 protein has been reported in cervical intraepithelial neoplasia (CIN) as well as cervical cancer. Such molecular biomarkers have been utilized for ancillary testing of liquid-based cytology specimens; however, their clinical application remains controversial. To detect CIN 2 or more advanced lesions, 153 liquid-based cytology (LBC) specimens were investigated to determine the physical status of the human papillomavirus (HPV) DNA by in situ hybridization (ISH) and to detect overexpression of the P16 protein by immunocytochemistry combined with HPV genotyping by polymerase chain reaction. The combination of ISH, P16 immunocytochemistry, and LBC showed high sensitivity (89.3%) as well as high specificity (92.6%). We confirmed the usefulness of P16 immunocytochemistry combined with ISH and HPV genotyping as ancillary molecular-biological tests of LBC specimens for identifying patients at high risk of cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. fujiit@sc.itc.keio.ac.jp
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujii
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Nobumaru
authors.initials: N
authors.lastname: Hirao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishio
authors.forename: Akiko
authors.initials: A
authors.lastname: Ohno
authors.forename: Katsumi
authors.initials: K
authors.lastname: Tsukazaki
authors.forename: Makio
authors.initials: M
authors.lastname: Mukai
authors.forename: Kaori
authors.initials: K
authors.lastname: Kameyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003584:Cytological Techniques / Q000379:methods*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000378:metabolism / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000378:metabolism / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins